Abstract

AIM To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model, with a focus on dry eye-like alterations. METHODS Male C57BL/6J mice (10–12 weeks old) were randomly assigned to control or restraint stress (RS) groups. The RS group underwent three intermittent 24-hour restraint sessions to induce depressive-like behavior. Behavioral testing, tear secretion measurement, and corneal Oregon Green Dextran (OGD) staining were performed. Postmortem analyses included histological evaluation of lacrimal glands, goblet cell quantification using periodic acid-Schiff staining, and assessment of key inflammatory and apoptotic markers: interleukin (IL)-17, matrix metalloproteinases (MMP)-3, MMP-9, IL-13, interferon (IFN)-γ, and cleaved caspase-3 and -8. RESULTS Repeated RS induced depression-like behavior and significant ocular surface changes. RS-treated mice showed increased corneal OGD uptake and upregulation of gene/protein expression of IL-17, MMP-3, and MMP-9 ( P <0.05). Goblet cell density and IL-13 protein expression were reduced, while IFN-γ protein expression was elevated ( P <0.05). Cleaved caspase-3 and -8 levels were significantly increased in both cornea and conjunctiva. Tear volume and lacrimal gland size were unchanged; however, mild inflammatory infiltration was observed in lacrimal glands. CONCLUSION Repeated RS leads to ocular surface inflammation and dry eye-like pathology, including corneal barrier disruption, goblet cell loss, and epithelial apoptosis. These findings suggest that depression contributes to the pathogenesis of dry eye disease via immune-mediated mechanisms.